caa a22 4500 445311533 CHVBK 20180317142631.0 cr unu---uuuuu 170323e20110101xx s 000 0 eng 10.1007/s11095-010-0123-9 doi (NATIONALLICENCE)springer-10.1007/s11095-010-0123-9 Microneedle-Based Intradermal Delivery Enables Rapid Lymphatic Uptake and Distribution of Protein Drugs [Elektronische Daten] [Alfred Harvey, Scott Kaestner, Diane Sutter, Noel Harvey, John Mikszta, Ronald Pettis] ABSTRACT: Purpose: The purpose of this research was to examine the pharmacokinetics (PK) of drug uptake for microneedle-based intradermal (ID) delivery of several classes of protein drugs compared to standard subcutaneous (SC) administration. Methods: Systemic absorption kinetics of various proteins were analyzed following microneedle-based ID delivery and standard injection methods in the swine model. Comparative PK data were determined using standard non-compartmental techniques based on blood serum levels. Results: Delivery of proteins using microneedles resulted in faster systemic availability, measured via tmax, and increased maximal drug concentration, Cmax, over SC delivery for all proteins tested. Some agents also exhibited increased bioavailability for the ID route. Imaging studies using reporter dyes showed rapid lymphatic-mediated uptake. Conclusions: Microneedle delivery is applicable to a wide variety of protein drugs and is capable of effective parenteral administration of therapeutic drug dosages. This delivery route alters absorption kinetics via targeting a tissue bed better perfused with lymphatic and blood vessels than the SC space. Microneedle delivery may afford various advantages, including a robust method to increase the absorption rate and bioavailability of proteins that have been challenging to deliver at therapeutic levels or with physiologically relevant profiles. Springer Science+Business Media, LLC, 2010 insulin nationallicence intradermal delivery nationallicence lymphatic uptake nationallicence microneedle nationallicence pharmacodynamics nationallicence pharmacokinetics nationallicence protein nationallicence AAALAC : Association for Assessment and Accreditation of Laboratory Animal Care nationallicence BG : Blood glucose nationallicence Cmax : Maximum blood concentration nationallicence IACUC : Institutional Animal Care and Use Committee nationallicence ICG : Intracardiac green dye nationallicence ID : Intradermal nationallicence IM : Intramuscular nationallicence IV : Intravenous nationallicence NIH : National Institutes of Health nationallicence NIR : Near infrared nationallicence PD : Pharmacodynamics nationallicence PK : Pharmacokinetics nationallicence rhGH : Recombinant human growth hormone nationallicence SC : Subcutaneous nationallicence SD : Standard deviation nationallicence SEM : Standard error of the mean nationallicence SWFI : Sterile water for injection nationallicence t1/2λz : Terminal half life nationallicence TB : Tuberculosis nationallicence tmax : Time to max blood concentration nationallicence TNFα : Tumor necrosis factor alpha nationallicence USDA : United States Department of Agriculture nationallicence VAP : Vascular access port nationallicence Harvey Alfred BD Technologies, 21 Davis Drive, 27709, Research Triangle Park, North Carolina, USA aut Kaestner Scott BD Technologies, 21 Davis Drive, 27709, Research Triangle Park, North Carolina, USA aut Sutter Diane BD Technologies, 21 Davis Drive, 27709, Research Triangle Park, North Carolina, USA aut Harvey Noel BD Technologies, 21 Davis Drive, 27709, Research Triangle Park, North Carolina, USA aut Mikszta John BD Technologies, 21 Davis Drive, 27709, Research Triangle Park, North Carolina, USA aut Pettis Ronald BD Technologies, 21 Davis Drive, 27709, Research Triangle Park, North Carolina, USA aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/1(2011-01-01), 107-116 0724-8741 28:1<107 2011 28 11095 https://doi.org/10.1007/s11095-010-0123-9 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-010-0123-9 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Harvey Alfred BD Technologies, 21 Davis Drive, 27709, Research Triangle Park, North Carolina, USA aut NATIONALLICENCE 700 1- Kaestner Scott BD Technologies, 21 Davis Drive, 27709, Research Triangle Park, North Carolina, USA aut NATIONALLICENCE 700 1- Sutter Diane BD Technologies, 21 Davis Drive, 27709, Research Triangle Park, North Carolina, USA aut NATIONALLICENCE 700 1- Harvey Noel BD Technologies, 21 Davis Drive, 27709, Research Triangle Park, North Carolina, USA aut NATIONALLICENCE 700 1- Mikszta John BD Technologies, 21 Davis Drive, 27709, Research Triangle Park, North Carolina, USA aut NATIONALLICENCE 700 1- Pettis Ronald BD Technologies, 21 Davis Drive, 27709, Research Triangle Park, North Carolina, USA aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/1(2011-01-01), 107-116 0724-8741 28:1<107 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer